Researchers build tiny living robots from human lung cells to deliver medicine.

Scientists have developed microscopic biological robots from human lung cells that can be programmed to move in specific ways. These tiny living machines, known as AggreBots, are constructed from clusters of cells and propelled by the beating of cilia, the hair-like structures that clear airways. This breakthrough in bio-hybrid robotics could pave the way for new medical therapies, including targeted drug delivery and tissue repair, using robots built from a patient’s own cells.

The research, conducted at Carnegie Mellon University and published in Science Advances, presents a new method for creating and controlling these biobots. Unlike previous biobots that relied on muscle tissue for movement, AggreBots use a novel engineering approach that allows for precise control over their locomotion. By arranging spheroids of lung stem cells, some with active cilia and some without, researchers can essentially create a “motor map” on the surface of the bot, directing its path. This level of control, combined with the inherent biocompatibility of the bots, opens up significant possibilities for their use inside the human body.

A New Engine for Biological Robots

Historically, the field of microscopic biobots has focused on using muscle fibers to generate movement. These bots would move through a process of contraction and relaxation, mimicking the way real muscles work. While effective to a degree, this method presented limitations. The Carnegie Mellon team, however, turned to a different biological mechanism for propulsion: cilia. Cilia are minuscule, hair-like appendages present on the surface of certain cells. In the human respiratory tract, their coordinated, wave-like beating is responsible for pushing mucus and trapped debris out of the lungs.

This same principle is used by microorganisms like the Paramecium to swim through water. The researchers recognized the potential of harnessing this natural, continuous propulsive force for a new class of biobots, which they have termed CiliaBots. The challenge, however, was not just making them move, but directing that movement in a predictable and useful manner. The innovation lies in controlling the placement and activity of the cilia to steer the biobot with a high degree of precision.

Designing for Precise Navigation

The key to controlling the AggreBots lies in their unique construction. The scientists grow lung stem cells into small, spherical clusters called spheroids. These spheroids are then fused together to build the larger biobot. To achieve controlled movement, the team combines spheroids that have functional, beating cilia with other spheroids that have been genetically modified to have non-functional cilia. By strategically placing these inactive spheroids, the researchers can create specific patterns of ciliary action on the bot’s surface.

Dhruv Bhattaram, the study’s first author, compared this method to steering a rowboat. By removing oars from one side or changing their position, one can alter the boat’s course. Similarly, by controlling where the propulsive cilia are located, the scientists can dictate how the AggreBot moves, whether in straight lines, tight loops, or other patterns. This assembly method provides a new dimension of design for bio-hybrid robots, allowing for customizable motility tailored to specific tasks.

Biocompatible and Personalized Medicine

One of the most significant advantages of the AggreBots is that they are made entirely from biological materials. This makes them naturally biodegradable and biocompatible, reducing the risk of adverse reactions when used inside the human body. Because they can be manufactured from a patient’s own stem cells, the potential for immune system rejection is minimized, opening the door for personalized medical treatments.

These tiny robots could one day be deployed to traverse complex environments within the body. Their precise motility is a key factor for navigating the human body to deliver drugs directly to a tumor, for example, or to assist in repairing damaged tissue. Associate Professor Xi Ren, who led the lab, emphasized that the ability to move with precision is critical in such a complex setting. The research provides a clear path for controlling how these microscopic agents navigate to perform their intended functions.

A Tool for Studying Disease

Beyond their therapeutic potential, AggreBots also offer a novel platform for medical research. Specifically, they could become powerful tools for studying ciliopathies—diseases caused by dysfunctional cilia. Conditions like primary ciliary dyskinesia and cystic fibrosis are linked to problems with ciliary function. By creating biobots with specific ciliary arrangements and observing their behavior, scientists can gain a better understanding of how these diseases affect the body at a cellular level.

This research could help in developing and testing new treatments for these and other related conditions. The ability to build these models from human cells provides a more accurate representation of human physiology compared to some animal models. This could accelerate the discovery of new therapeutic strategies and deepen our understanding of cellular mechanics and human health.

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